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Efficacy and safety of efalizumab in a large cohort of patients with moderate to severe plaque psoriasis: pooled results from randomized phase III trials
POSTER DISCUSSION SESSION 491—PSORIASIS Psoriasis & Other Papulosquamous Disorders P1 A POOLED ANALYSIS OF STUDIES WITH A NEW CALCIPOTRIENE/BETAMETHASONE TWO-COMPOUND PRODUCT IN PSORIASIS VULGARIS Alex V Anstey, MBBS, MD, Royal Gwent Hospital, Newport, Wales, Adrian Bibby, BSc, LEO Pharma, Princes Risborough, England An ointment containing a combination of calcipotriene and betamethasone dipropionate has been formulated. Studies have shown efficacy superior to that of each component used as mono-therapy in terms of reduction in PASI and investigators’ and patients’ global assessments. The US National Psoriasis Foundation has recently defined treatment success of 50% or more improvement in PASI (PASI 50)as a useful tool for evaluating clinical effect relevant for the patients, and recommends reporting this value to permit comparisons across studies. Therefore PASI 50 has been calculated based on trials performed on the twocompound product (n ⫽ 1534): 81% of patients achieved this definition of treatment success after 4 weeks treatment. Other studies using PASI 50 have reported success rates of 59% with efalizumab (n ⫽ 369), 56% with alefacept (n ⫽ 367) and 74% with etanercept (n ⫽ 164) after 12 weeks treatment. This measure of PASI 50 further confirms the effectiveness of the new two-compound (calcipotriene and betamethasone) product. Dr Anstey is an investigator for studies sponsored by LEO Pharma. Adrian Bibby is an employee of LEO Pharma. LEO Pharma is the manufacturer of the commercial product discussed in this poster. 100 percent sponsored by LEO Pharma
P3 RETROSPECTIVE ANALYSIS OF ADVERSE EFFECTS AND COMORBIDITIES IN PATIENTS ON SYSTEMIC PSORIASIS THERAPY Dan Pearce, MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Rajesh Balkrishnan, PhD, Division of Management and Policy Sciences, University of Texas School of Public Health, Houston, TX, United States, Wei Lang, PhD, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Background: For patients with severe psoriasis there are numerous treatment options that have documented efficacy in clinical trials. Relative to topical therapies, these treatments are typically more aggressive, systemic medications that are sometimes associated with adverse events. Also, a significant number of patients with severe psoriasis suffer from comorbid diseases. These comorbidities sometimes result in end organ dysfunction. Therefore adverse effects of systemic psoriasis therapy may have particularly severe consequences in patients with comorbidities. Purpose: The purpose of this study is to evaluate the prevalence of adverse effects associated with certain systemic treatments for severe psoriasis. Additionally, major comorbid disease states will be examined in patients with psoriasis. Methods: A retrospective chart review of more than 500 patients from an academic dermatology practice was performed. The patients were selected by ICD-9 coding for psoriasis and were included if having ever received systemic therapy for psoriasis. Data on adverse events associated with systemic treatments were compiled. Results: It was found that among patients on systemic therapy for advanced psoriasis adverse effects were present in nearly all treatment groups with the highest frequency observed in patients on methotrexate (4% GI dysfunction). Additionally, the prevalence of common comorbid disease states in all patients with psoriasis was common and ranged from 2% (renal dysfunction) to 31% (hypertension). Discussion: For patients with severe psoriasis systemic therapy is often needed. Traditional psoriasis therapies are associated with significant adverse events in some patients. Furthermore, patients with severe psoriasis often suffer from comorbid diseases and the impact of adverse effects associated with traditional systemic therapy could potentially exacerbate pre-existing organ dysfunction. New systemic treatment options with improved side effect profiles are needed for the treatment of severe psoriasis, particularly in patients with comorbid disease states. Disclosure not available at press time. This study has been funded by Glaxo-Smith Kline
P2 ADALIMUMAB EFFICACY AND SAFETY IN PATIENTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS: PRELIMINARY FINDINGS FROM A 12-WEEK DOSE-RANGING TRIAL Diana M Chen, MD, Abbott Laboratories, Abbott Park, IL, United States, Kenneth Gordon, MD, Loyola University, Stritch School of Medicine, Maywood, IL, United States, Craig Leonardi, MD, Saint Louis University, St. Louis, MO, United States, M. Alan Menter, MD, Baylor University Medical Center and University of Texas Southwestern Medical School, Dallas, TX, United States Adalimumab is a human monoclonal IgG1 antibody containing only human peptide sequences which is approved for use in the US in adults with rheumatoid arthritis. It binds specifically to soluble and membrane-bound tumor necrosis factor-alpha (TNF-alpha), thereby neutralizing the biological activities of this cytokine. In psoriasis, TNF-alpha expression is notably increased in psoriatic plaques. The efficacy and safety of two dose levels of adalimumab in the treatment of psoriasis was determined in a randomized, double blind, placebo-controlled trial (M02-528). In this phase II multicenter trial conducted in the US and Canada, the safety and efficacy of 12 weeks of adalimumab therapy was compared to placebo in 148 adult men and women with moderate to severe chronic plaque psoriasis. Inclusion criteria consisted of a minimum of 5% body surface area involvement and no prior history of TNF-alpha antagonist therapy. Over 30% of patients had been treated with systemic methotrexate, cyclosporine, or retinoids, more than one-third had received phototherapy, and greater than 70% of patients had applied topical therapy in the 12 months prior to study entry. Preliminary demographic information of the study population include a mean age of 45 years (range 20 to 86 years), 66% men and 34% women, ⬇90% Caucasian, mean duration of psoriasis of 21 years, and a mean baseline Psoriasis Area Severity Index (PASI) score of 15. Patients were randomized to receive adalimumab administered subcutaneously 40 mg every other week, 40 mg weekly, or placebo. The proportion of patients with at least a 75% reduction in PASI score compared to baseline (ⱖPASI 75 improvement) was assessed at week 12. The time to achieving ⱖ PASI 75 improvement was determined and the proportion of patients who were clear or almost clear of their psoriasis at the end of treatment assessed. The study is fully enrolled and preliminary efficacy and safety findings of this trial will be presented at the meeting. Diana Chen, MD, is employed by Abbott Laboratories. Kenneth Gordon, MD, has received research support from Abbott Laboratories and will discuss the use of adalimumab for psoriasis, a disease for which it does not have FDA approval. Craig Leonardi, MD, has no financial interest in Abbott Laboratories or its subsidiaries. M. Alan Menter, MD, has received research support, consultancies, and honoraria from Abbott Laboratories, Allergan, Allermed, Amgen, Biogen, Centocor, Connetics, Corixa, Fujisawa, GlaxoSmithKline, Genentech, Inamed, Lumenis, Novartis, Otsuka, Photocure, Scirex, Serono, and Thermosurgery. 100 percent sponsored by Abbott Laboratories
MARCH 2004
P4 EFFICACY AND SAFETY OF EFALIZUMAB IN A LARGE COHORT OF PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS: POOLED RESULTS FROM RANDOMIZED PHASE III TRIALS Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States, David Pariser, MD, Virginia Clinical Research and Eastern Virginia Medical School, Norfolk, VA, United States, Richard Langley, MD, Dalhousie University Medical School, Halifax, Nova Scotia, Canada, Ivor Caro, MD, Genentech, South San Francisco, CA, United States Despite many treatment options for plaque psoriasis, dermatologists face challenges when treating their patients with moderate to severe disease due to the potential for cumulative toxicity with traditional systemic therapies, inconvenience, and dissatisfaction with current options. These limitations, coupled with knowledge regarding the immunopathogenesis of psoriasis, prompted the development of biologic therapies. Efalizumab, a humanized monoclonal IgG1 antibody, is a targeted T-cell modulator that has demonstrated efficacy and safety in various Phase III randomized, placebo-controlled trials. In 3 Phase III trials, all efficacy endpoints were statistically significant with consistent outcomes. Results for Weeks 1-12, for which study designs were similar, were pooled to profile the efficacy and safety in a large cohort of 1,651 patients with moderate to severe plaque psoriasis, the largest cohort of psoriasis patients treated with a biologic therapy to date. Following a 2-4 week washout period, patients received efalizumab 1 mg/kg/wk (n ⫽ 763), efalizumab 2 mg/kg/wk (n ⫽ 409; 2 of 3 studies only), or placebo (n ⫽ 479) during Weeks 1-12. The treatment groups were well balanced at baseline. In both efalizumab dose groups, 28% of patients achieved at least 75% improvement in Psoriasis Area Severity Index (PASI-75) at Week 12, relative to baseline (vs 4% placebo; P ⬍ .001, both comparisons). At Week 12, 57% and 55% of patients in the efalizumab 1 mg/kg- and 2 mg/kg-dose groups achieved a PASI-50 response (vs 15% placebo; P ⬍ .001, both comparisons). The mean percent PASI improvement at Week 12 was highly significant in the efalizumab-treated patients relative to placebo-treated patients at Week 2 (P ⫽ .0001). Efalizumab was well tolerated; the most common adverse events (reported in ⱖ5% of all patients) included headache, nonspecific infection (e.g., common colds), nausea, chills, pain asthenia, myalgia, pharyngitis, diarrhea, accidental injury, and rhinitis. The adverse events were generally mild to moderate in intensity. The majority of the most frequently reported adverse events occurred with the first two efalizumab doses and were classified as acute. By the third dose, the incidence of acute adverse events in the efalizumab and placebo groups was comparable. The rapid onset of PASI improvement, efficacy, safety, and convenience of once-weekly dosing suggest that efalizumab will represent a viable therapeutic option for moderate to severe psoriasis. Author is consultant for Genentech, Inc.
J AM ACAD DERMATOL
P1
P3 RETROSPECTIVE ANALYSIS OF ADVERSE EFFECTS AND COMORBIDITIES IN PATIENTS ON SYSTEMIC PSORIASIS THERAPY Dan Pearce, MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Rajesh Balkrishnan, PhD, Division of Management and Policy Sciences, University of Texas School of Public Health, Houston, TX, United States, Wei Lang, PhD, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Background: For patients with severe psoriasis there are numerous treatment options that have documented efficacy in clinical trials. Relative to topical therapies, these treatments are typically more aggressive, systemic medications that are sometimes associated with adverse events. Also, a significant number of patients with severe psoriasis suffer from comorbid diseases. These comorbidities sometimes result in end organ dysfunction. Therefore adverse effects of systemic psoriasis therapy may have particularly severe consequences in patients with comorbidities. Purpose: The purpose of this study is to evaluate the prevalence of adverse effects associated with certain systemic treatments for severe psoriasis. Additionally, major comorbid disease states will be examined in patients with psoriasis. Methods: A retrospective chart review of more than 500 patients from an academic dermatology practice was performed. The patients were selected by ICD-9 coding for psoriasis and were included if having ever received systemic therapy for psoriasis. Data on adverse events associated with systemic treatments were compiled. Results: It was found that among patients on systemic therapy for advanced psoriasis adverse effects were present in nearly all treatment groups with the highest frequency observed in patients on methotrexate (4% GI dysfunction). Additionally, the prevalence of common comorbid disease states in all patients with psoriasis was common and ranged from 2% (renal dysfunction) to 31% (hypertension). Discussion: For patients with severe psoriasis systemic therapy is often needed. Traditional psoriasis therapies are associated with significant adverse events in some patients. Furthermore, patients with severe psoriasis often suffer from comorbid diseases and the impact of adverse effects associated with traditional systemic therapy could potentially exacerbate pre-existing organ dysfunction. New systemic treatment options with improved side effect profiles are needed for the treatment of severe psoriasis, particularly in patients with comorbid disease states. Disclosure not available at press time. This study has been funded by Glaxo-Smith Kline
P2 ADALIMUMAB EFFICACY AND SAFETY IN PATIENTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS: PRELIMINARY FINDINGS FROM A 12-WEEK DOSE-RANGING TRIAL Diana M Chen, MD, Abbott Laboratories, Abbott Park, IL, United States, Kenneth Gordon, MD, Loyola University, Stritch School of Medicine, Maywood, IL, United States, Craig Leonardi, MD, Saint Louis University, St. Louis, MO, United States, M. Alan Menter, MD, Baylor University Medical Center and University of Texas Southwestern Medical School, Dallas, TX, United States Adalimumab is a human monoclonal IgG1 antibody containing only human peptide sequences which is approved for use in the US in adults with rheumatoid arthritis. It binds specifically to soluble and membrane-bound tumor necrosis factor-alpha (TNF-alpha), thereby neutralizing the biological activities of this cytokine. In psoriasis, TNF-alpha expression is notably increased in psoriatic plaques. The efficacy and safety of two dose levels of adalimumab in the treatment of psoriasis was determined in a randomized, double blind, placebo-controlled trial (M02-528). In this phase II multicenter trial conducted in the US and Canada, the safety and efficacy of 12 weeks of adalimumab therapy was compared to placebo in 148 adult men and women with moderate to severe chronic plaque psoriasis. Inclusion criteria consisted of a minimum of 5% body surface area involvement and no prior history of TNF-alpha antagonist therapy. Over 30% of patients had been treated with systemic methotrexate, cyclosporine, or retinoids, more than one-third had received phototherapy, and greater than 70% of patients had applied topical therapy in the 12 months prior to study entry. Preliminary demographic information of the study population include a mean age of 45 years (range 20 to 86 years), 66% men and 34% women, ⬇90% Caucasian, mean duration of psoriasis of 21 years, and a mean baseline Psoriasis Area Severity Index (PASI) score of 15. Patients were randomized to receive adalimumab administered subcutaneously 40 mg every other week, 40 mg weekly, or placebo. The proportion of patients with at least a 75% reduction in PASI score compared to baseline (ⱖPASI 75 improvement) was assessed at week 12. The time to achieving ⱖ PASI 75 improvement was determined and the proportion of patients who were clear or almost clear of their psoriasis at the end of treatment assessed. The study is fully enrolled and preliminary efficacy and safety findings of this trial will be presented at the meeting. Diana Chen, MD, is employed by Abbott Laboratories. Kenneth Gordon, MD, has received research support from Abbott Laboratories and will discuss the use of adalimumab for psoriasis, a disease for which it does not have FDA approval. Craig Leonardi, MD, has no financial interest in Abbott Laboratories or its subsidiaries. M. Alan Menter, MD, has received research support, consultancies, and honoraria from Abbott Laboratories, Allergan, Allermed, Amgen, Biogen, Centocor, Connetics, Corixa, Fujisawa, GlaxoSmithKline, Genentech, Inamed, Lumenis, Novartis, Otsuka, Photocure, Scirex, Serono, and Thermosurgery. 100 percent sponsored by Abbott Laboratories
MARCH 2004
P4 EFFICACY AND SAFETY OF EFALIZUMAB IN A LARGE COHORT OF PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS: POOLED RESULTS FROM RANDOMIZED PHASE III TRIALS Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States, David Pariser, MD, Virginia Clinical Research and Eastern Virginia Medical School, Norfolk, VA, United States, Richard Langley, MD, Dalhousie University Medical School, Halifax, Nova Scotia, Canada, Ivor Caro, MD, Genentech, South San Francisco, CA, United States Despite many treatment options for plaque psoriasis, dermatologists face challenges when treating their patients with moderate to severe disease due to the potential for cumulative toxicity with traditional systemic therapies, inconvenience, and dissatisfaction with current options. These limitations, coupled with knowledge regarding the immunopathogenesis of psoriasis, prompted the development of biologic therapies. Efalizumab, a humanized monoclonal IgG1 antibody, is a targeted T-cell modulator that has demonstrated efficacy and safety in various Phase III randomized, placebo-controlled trials. In 3 Phase III trials, all efficacy endpoints were statistically significant with consistent outcomes. Results for Weeks 1-12, for which study designs were similar, were pooled to profile the efficacy and safety in a large cohort of 1,651 patients with moderate to severe plaque psoriasis, the largest cohort of psoriasis patients treated with a biologic therapy to date. Following a 2-4 week washout period, patients received efalizumab 1 mg/kg/wk (n ⫽ 763), efalizumab 2 mg/kg/wk (n ⫽ 409; 2 of 3 studies only), or placebo (n ⫽ 479) during Weeks 1-12. The treatment groups were well balanced at baseline. In both efalizumab dose groups, 28% of patients achieved at least 75% improvement in Psoriasis Area Severity Index (PASI-75) at Week 12, relative to baseline (vs 4% placebo; P ⬍ .001, both comparisons). At Week 12, 57% and 55% of patients in the efalizumab 1 mg/kg- and 2 mg/kg-dose groups achieved a PASI-50 response (vs 15% placebo; P ⬍ .001, both comparisons). The mean percent PASI improvement at Week 12 was highly significant in the efalizumab-treated patients relative to placebo-treated patients at Week 2 (P ⫽ .0001). Efalizumab was well tolerated; the most common adverse events (reported in ⱖ5% of all patients) included headache, nonspecific infection (e.g., common colds), nausea, chills, pain asthenia, myalgia, pharyngitis, diarrhea, accidental injury, and rhinitis. The adverse events were generally mild to moderate in intensity. The majority of the most frequently reported adverse events occurred with the first two efalizumab doses and were classified as acute. By the third dose, the incidence of acute adverse events in the efalizumab and placebo groups was comparable. The rapid onset of PASI improvement, efficacy, safety, and convenience of once-weekly dosing suggest that efalizumab will represent a viable therapeutic option for moderate to severe psoriasis. Author is consultant for Genentech, Inc.
J AM ACAD DERMATOL
P1